Infected Ruptured Pseudo-aneurysm in Descending Aorta; a Case Report.

Aortitis is the inflammation of the aortic wall. It can be caused by both infectious and non-infectious etiologies. Mycotic aneurysm is a rare, serious medical condition and typically requires prompt treatment with antibiotics, surgical intervention, or endovascular procedures to prevent rupture and complications. Here we reported, a 66-year-old male patient with a medical history of diabetes and hypertension, who presented to the emergency department (ED) with left-sided hemiplegia. Brain magnetic resonance imaging (MRI) revealed infarction in the right parietooccipital and left occipital lobes, demonstrating an embolic pattern. laboratory analysis revealed elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and white blood cell (WBC). In order to investigate the possibility of sepsis, a non-contrast chest computed tomography (CT) scan was performed, which showed a soft tissue density surrounded by gas in the posterior mediastinum; for which the rupture of esophagus and infected aorta pseudoaneurysm were among differential diagnoses. To confirm the diagnosis, CT angiography was ordered. The infected ruptured pseudo-aneurysm(s) was confirmed and patient underwent thoracotomy surgery.

Prenatal diagnosis of Sex determining region Y -box transcription factor 2 anophthalmia syndrome caused by germline mosaicism using next-generation sequencing: A case report.

Background: Sex determining region Y box transcription factor 2 (SOX2) mutations lead to bilateral anophthalmia with autosomal dominant human inheritance. SOX2 mutations could result in severe ocular phenotypes usually associated with variable systemic defects. Most patients described with SOX2 anophthalmia syndrome possessed de novo mutations in this gene. Case Presentation: In this case report, we describe 2 brothers with mental retardation and bilateral anophthalmia caused due to SOX2 germline mosaicism in unaffected parents. Next-generation DNA sequencing was carried out to determine the family's possible cause of genetic mutation. Sanger sequencing was performed on the patients and their parents. Prenatal diagnosis was done in both pregnancies of the older brother's wife via chorionic villus sampling. A novel heterozygous pathogenic frameshift deletion variant (exon1:c.58_80del:p.G20fs) was identified in the SOX2 gene, which was confirmed by Sanger sequencing in both affected brothers and did not exist in healthy parents, indicating germline mosaicism. Conclusion: Most SOX2 mutations known look to arise de novo in probands and are diagnosed through anophthalmia or microphthalmia. Prenatal diagnosis should be offered to healthy parents with a child with SOX2 mutation every pregnancy.

WWFedCBMIR: World-Wide Federated Content-Based Medical Image Retrieval.

The paper proposes a federated content-based medical image retrieval (FedCBMIR) tool that utilizes federated learning (FL) to address the challenges of acquiring a diverse medical data set for training CBMIR models. CBMIR is a tool to find the most similar cases in the data set to assist pathologists. Training such a tool necessitates a pool of whole-slide images (WSIs) to train the feature extractor (FE) to extract an optimal embedding vector. The strict regulations surrounding data sharing in hospitals makes it difficult to collect a rich data set. FedCBMIR distributes an unsupervised FE to collaborative centers for training without sharing the data set, resulting in shorter training times and higher performance. FedCBMIR was evaluated by mimicking two experiments, including two clients with two different breast cancer data sets, namely BreaKHis and Camelyon17 (CAM17), and four clients with the BreaKHis data set at four different magnifications. FedCBMIR increases the F1 score (F1S) of each client from 96% to 98.1% in CAM17 and from 95% to 98.4% in BreaKHis, with 11.44 fewer hours in training time. FedCBMIR provides 98%, 96%, 94%, and 97% F1S in the BreaKHis experiment with a generalized model and accomplishes this in 25.53 fewer hours of training.

The Efficacy of Long-Pulsed, 1064-nm Nd:YAG Laser Versus Aluminum Chloride 20% Solution in the Treatment of Axillary Hyperhidrosis.

Introduction: Hyperhidrosis (HH) refers to uncontrollable excessive sweating that has a significant negative impact on the quality of life. The aim of this study was to compare the efficacy and safety of the long-pulsed, 1064-nm Nd:YAG laser and aluminum chloride (ALCL3 ) 20% solution in axillary HH treatment. Methods: In this single-center, within-patient comparison clinical trial, 12 patients with axillary HH were treated monthly for 3 to 4 consecutive sessions with the long-pulsed, 1064-nm Nd:YAG laser system on one axilla, while the contralateral axilla was treated with ALCL3 20 % by the patient. Treatment response was evaluated by comparing the area of sweating at the end of each session and 6 months after treatment termination using the iodine starch test. Results: Both treatments led to the reduction of HH from baseline with the mean area of sweating reduced from 109.3±36.6 to 38.3±19.8 and from 92.5±31.6 to 35.6±17.1 in laser- and ALCL3-treated axilla respectively (Both P<0.001). In the 6-month follow-up, the area of sweating was 60.6±29.2 in the laser-treated armpit and 78.3±23.6 in the ALCL3-treated side, which were 45% and 14.4% lower compared to the baseline respectively. Adverse events were temporary, and none caused each of the treatments to be discontinued. Conclusion: The long-pulsed, 1064-nm Nd:YAG laser with hair reduction setting can stand as a potential therapeutic option for axillary HH since it is as effective as ALCL3. The therapeutic effect is superior in the long term for the laser; nevertheless, the beneficial effect of both treatments may lessen the following treatment cessation.

What we think about professional and unprofessional behaviors: differences between the perception of clinical faculty members and medical students.

INTRODUCTION: Differences in the viewpoints of clinical faculty members and medical students about prioritizing professional norms accepted by the professional community and lack of alignment of these views can lead to distortion of understanding, problems in learning and assessment of professionalism, and failure in students' professional identity formation. This study aimed to identify the differences in viewpoints of clinical faculty members and medical students about prioritizing the importance and prevalence of professional and unprofessional behaviors among undergraduate medical students. METHODS: A multi-stage qualitative study was conducted at Tehran University of Medical Sciences during 2020-2021. At first, a systematic search was conducted to identify professional and unprofessional behaviors using the directional content analysis method. A panel of experts was formed to check the codes obtained from reviewing the literature and to evaluate its compliance with the context. Then, the modified nominal group technique sessions were held with clinical faculty members and medical students to strengthen the codes extracted from the studies and systematically integrate their views to achieve a comprehensive list of professional and unprofessional behaviors in accordance with the context. Finally, a consensus was made among them about prioritizing the importance and prevalence of these behaviors in undergraduate medical students. RESULTS: A total of 490 codes of professional behaviors and 595 unprofessional behavior codes were identified in the literature review. In the following sessions of the modified nominal group, 13 clinical faculty members listed 105 codes of professional and unprofessional behaviors, and 51 medical students also listed 313 codes. The results of the modified nominal group technique showed that the faculty members reported the importance of unprofessional behaviors higher than professional ones. At the same time, students rated the importance of professional behaviors higher than unprofessional ones. Both faculty members and students rate the prevalence of professional behaviors as high and the prevalence of unprofessional behaviors as low. CONCLUSION: The results showed a difference of views between clinical faculty members and medical students about prioritizing professional and unprofessional behaviors. It is essential to align their viewpoints to understand, learn and value professionalism to develop a professional identity.

Deep Learning for Skin Melanocytic Tumors in Whole-Slide Images: A Systematic Review.

The rise of Artificial Intelligence (AI) has shown promising performance as a support tool in clinical pathology workflows. In addition to the well-known interobserver variability between dermatopathologists, melanomas present a significant challenge in their histological interpretation. This study aims to analyze all previously published studies on whole-slide images of melanocytic tumors that rely on deep learning techniques for automatic image analysis. Embase, Pubmed, Web of Science, and Virtual Health Library were used to search for relevant studies for the systematic review, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Articles from 2015 to July 2022 were included, with an emphasis placed on the used artificial intelligence methods. Twenty-eight studies that fulfilled the inclusion criteria were grouped into four groups based on their clinical objectives, including pathologists versus deep learning models (n = 10), diagnostic prediction (n = 7); prognosis (n = 5), and histological features (n = 6). These were then analyzed to draw conclusions on the general parameters and conditions of AI in pathology, as well as the necessary factors for better performance in real scenarios.

Pre-Implantation Genetic Testing for Monogenic Disorders (PGT-M) in A Family with A Novel Mutation in DPAGT1 Gene.

Congenital disorders of glycosylation (CDG) are a heterogeneous group of systemic disorders characterized by defects in glycosylation of lipids and proteins. One of the rare subtypes of CDG is CDG-Ij (MIM # 608093), which is caused by pathogenic mutations in DPAGT1, a gene encoding UDP-N-acetylglucosaminedolichyl-phosphate N-acetylglucosaminephosphotransferase enzyme. This enzyme catalyzes the first step of oligosaccharide synthesis in glycoprotein biosynthesis pathway. Preimplantation genetic testing for monogenic disorders (PGT-M) is a diagnostic technique that can reveal the genetic profile of embryos before implantation phase of in vitro fertilization (IVF). Currently, this approach is performed using next generation sequencing (NGS) technology. Herein, with the help of whole-exome and Sanger sequencing, we detected a novel missense mutation (NM_001382, c.1217 A>G) in DPAGT1 gene in two families with consanguineous marriage. Using different online bioinformatics tools including MutationTaster, I-Mutant v2.0, T- Coffee, and CADD v1.0, this mutation was predicted pathogen. Finally, after performing PGT-M followed by successful pregnancy, a normal child was born in one of these families. In conclusion, we identified a novel pathogenic mutation in DPAGT1 in a family with multiple members affected by CDG, which extends the range of pathogenic variants associated with CDG and therefore facilitates early detection of the disease.

Distribution of Class 1-3 Integrons in Carbapenem-Resistant Pseudomonas aeruginosa Isolated from Inpatients in Shiraz, South of Iran.

BACKGROUND: Health-care-associated infection (HAI) is effect on patients for the time of staying in the hospital. Opportunistic pathogens including Pseudomonas aeruginosa are the most dangerous biological agents in nosocomial infections. This study aimed to assess the prevalence of 3 classes of integrons carrying to carbapenem resistance in P. aeruginosa strains collected from Nemazee hospital. METHODS: This cross-sectional study was conducted on clinical P. aeruginosa isolates were collected from Nemazee hospital. The identification of the isolates was performed by routine biochemical tests. Antimicrobial sensitivity testing was determined using the disk diffusion method against imipenem and meropenem. The int1, int2 and int3 genes were detected using the polymerase chain reaction (PCR). RESULTS: Seventy-five clinical isolates of P. aeruginosa were recovered from various clinical infections. A carbapenem-resistant phenotype was detected in 42.7% (imipenem) and 29.3% (meropenem) of isolates. As the PCR results, 48 (64%) and 15 (20%) isolates were identified as being positive for class 1 and class 2 integrons, respectively. Class 3 integrons were not found among the studied isolates. CONCLUSIONS: Our data demonstrate the importance of class 1 and 2 integrons in carbapenem resistant P. aeruginosa strains. Therefore, integrons play an important role in acquisition and dissemination of carbapenem resistance genes among these pathogens, so, management of infection control policies and the appropriate use of antibiotics is essential for control the spreading of antibiotics resistance genes.

Biallelic variants in TMEM222 cause a new autosomal recessive neurodevelopmental disorder.

PURPOSE: To elucidate the novel molecular cause in families with a new autosomal recessive neurodevelopmental disorder. METHODS: A combination of exome sequencing and gene matching tools was used to identify pathogenic variants in 17 individuals. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and subcellular localization studies were used to characterize gene expression profile and localization. RESULTS: Biallelic variants in the TMEM222 gene were identified in 17 individuals from nine unrelated families, presenting with intellectual disability and variable other features, such as aggressive behavior, shy character, body tremors, decreased muscle mass in the lower extremities, and mild hypotonia. We found relatively high TMEM222 expression levels in the human brain, especially in the parietal and occipital cortex. Additionally, subcellular localization analysis in human neurons derived from induced pluripotent stem cells (iPSCs) revealed that TMEM222 localizes to early endosomes in the synapses of mature iPSC-derived neurons. CONCLUSION: Our findings support a role for TMEM222 in brain development and function and adds variants in the gene TMEM222 as a novel underlying cause of an autosomal recessive neurodevelopmental disorder.

Pre-implantation genetic diagnosis in an Iranian family with a novel mutation in MUT gene.

BACKGROUND: Methylmalonic acidemia (MMA), which is an autosomal recessive metabolic disorder, is caused by mutations in methylmalonyl-CoA mutase (MUT) gene. As a result, the conversion of methylmalonyl-CoA to succinyl-CoA is impaired in this disorder, leading to a wide range of clinical manifestations varying from no signs or symptoms to severe lethargy and metabolic crisis in newborn infants. Since identification of novel mutations in MUT gene can help discover the exact pathogenesis of MMA and also use these disease-causing mutations in prenatal diagnosis, this study was conducted to uncover the possible mutations in an Iranian couple with a deceased offspring clinically diagnosed as having organic acidemia. Moreover, to prevent the occurrence of the mutation in the next pregnancy, we took the advantage of pre-implantation genetic diagnosis (PGD), which resulted in a successful pregnancy. CASE PRESENTATION: The affected individual was a 15-month-old boy who passed away due to aspiration pneumonia. The child presented at the age of 3 months with lethargy, protracted vomiting, hypotonia, and decreased level of consciousness. To find the mutated gene, Next Generation Sequencing (NGS) was performed as carrier testing for the parents and the results revealed a novel (private) heterozygous missense mutation in MUT gene (c.1055A > G, p.Q352R). After performing PGD on three blastomeres, one was identified as being homozygous wild-type that was followed by successful pregnancy. CONCLUSIONS: Our study identified a novel, deleterious, heterozygous missense mutation in MUT gene in a couple and helps to consider the genetic counselling and prenatal diagnosis more seriously for this family with clinical phenotypes of organic acidemia.

Expanding the molecular and clinical phenotypes of FUT8-CDG.

Pathogenic variants in the Golgi localised alpha 1,6 fucosyltransferase, FUT8, cause a rare inherited metabolic disorder known as FUT8-CDG. To date, only three affected individuals have been reported presenting with a constellation of symptoms including intrauterine growth restriction, severe delays in growth and development, other neurological impairments, significantly shortened limbs, respiratory complications, and shortened lifespan. Here, we report an additional four unrelated affected individuals homozygous for novel pathogenic variants in FUT8. Analysis of serum N-glycans revealed a complete lack of core fucosylation, an important diagnostic biomarker of FUT8-CDG. Our data expands both the molecular and clinical phenotypes of FUT8-CDG and highlights the importance of identifying a reliable biomarker for confirming potentially pathogenic variants.

Case Report: Expanding the Genetic and Phenotypic Spectrum of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder caused by biallelic mutations in the SACS gene. Once thought to be limited to Charlevoix-Saguenay region of Quebec, recent evidence has indicated that this disorder is present worldwide. It is classically characterized by the triad of ataxia, pyramidal involvement, and axonal-demyelinating sensorimotor neuropathy. However, diverse clinical features have been reported to be associated with this disorder. In this report, we present the first Iranian family affected by ARSACS with unique clinical features (mirror movements, hypokinesia/bradykinesia, and rigidity) harboring a novel deletion mutation in the SACS gene. Our findings expand the genetic and phenotypic spectrum of this disorder.

Identification of novel microsatellite markers flanking GJB2 gene in order to use in preimplantation genetic diagnosis of hearing loss: A comparison of whole-genome amplification and semi-nested PCR.

Hearing loss is the most prevalent sensorineural disorder which can be caused by genetic factors in more than half of the cases. GJB2 mutations with the frequency of 18.7% are the most common cause of autosomal recessive non-syndromic hearing loss (ARNSHL) in the Iranian population. The aim of the current study was to genotype 100 healthy individuals for eight microsatellite markers flanking the GJB2 gene, and to study markers on ten blastomeres using semi-nested PCR and Whole-genome amplification (WGA). All microsatellite markers within 1 Mb flanking the GJB2 gene were identified. From the identified markers, four with potentially high heterozygosity values were selected. The heterozygosity indices of four newly discovered markers and four previously reported markers were calculated. The markers and the GJB2 gene were also validated on single lymphocytes and blastomeres. Totally, 77 alleles were observed in eight loci. D13S046 showed the highest polymorphism and D13S141 showed the lowest. The observed heterozygosities of all markers, except D13S141, were higher than 50%. All single cells were genotyped successfully by the two techniques. Our findings indicate a high degree of polymorphism of the selected markers. Due to the high rate of successful amplification of markers in all ten blastomeres and the low level of allelic drop out (ADO), a combination of these eight microsatellite markers in conjunction with direct mutation detection is suggested for performing preimplantation genetic diagnosis (PGD) of hearing loss due to GJB2 mutations.

HIV-1 Tat protein attenuates the clinical course of experimental autoimmune encephalomyelitis (EAE).

A growing body of evidence has shown that the human immunodeficiency virus (HIV) infection is associated with a significantly decreased risk of developing multiple sclerosis (MS) in patients with acquired immunodeficiency virus (AIDS). It is thought that two mechanisms are in charge of protection against MS, which include immunosuppression induced by chronic HIV infection (depletion of CD4 + T cells) and antiretroviral medications. HIV-1 encodes several regulatory (Tat and Rev) and accessory (Vpr, Vif, Vpu, and Nef) proteins that have immunosuppressive and immunomodulatory properties. HIV-1 Tat protein is a strongly immunosuppressive agent and can cross the blood-brain barrier (BBB). In this study, we examined the effect of HIV-1 Tat, which is classified into clade B and C, on inflammation, gliosis, apoptosis, and behavioral function in a murine model of MS called experimental autoimmune encephalomyelitis (EAE). For this aim, mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55), followed by pertussis toxin to induce paralysis in EAE mice. After the induction of EAE in mice, the animals intraperitoneally received serial doses of HIV-1 Tat clade B and C (5, 10, and 20 µg/kg body weight) when the early clinical manifestations of EAE were initiated. The results showed that the administration of both clades of the Tat protein led to a marked decrease in the clinical score of EAE mice, as well as improvement in motor-neuron functions. In line with this, Tat considerably reduced the number of apoptotic cells in the sacral region of the spinal cord through the upregulation expression of the Bcl-2 protein. Besides, proinflammatory cytokines such as, IFN-γ, TNF-α, IL-6, and IL-17 were significantly diminished in the serum and spinal cord of EAE mice receiving HIV-1 Tat clade B and C. Conversely, anti-inflammatory cytokines, including IL-10 and IL-4 were elevated in the serum and spinal cord of EAE mice receiving HIV Tat clade B and C when compared with the control group. The immunohistochemical analysis indicated that HIV-1 Tat clade B and C mitigated microgliosis and astrogliosis. The flow cytometry analysis demonstrated that the number of Th1 and Th17cells was significantly decreased in response to TAT administration while the frequency of Th2 cells was markedly increased in the peripheral blood of mice with EAE without influencing the number of T regulatory cells (CD4 + CD25 + forkhead box protein 3 + ). It seems that HIV-1 Tat could be a bona fide therapeutic protein for the alleviation of MS since it has beneficial roles in the suppression of neuroinflammation in MS pathology.

A comparative study on generating hydroxyl radicals by single and two-frequency ultrasound with gold nanoparticles and protoporphyrin IX.

Sonodynamic therapy (SDT) is a new manner of killing cancer cells based on the cytotoxic interactions of ultrasound with sonosensitizing agents. It is shown that gold nanoparticles (GNPs) increase the efficiency of cavitation activity of ultrasound. In this study the influence of a single and/or two frequencies of ultrasound waves to generate hydroxyl radicals (·OH) was assessed in the presence of protoporphyrin IX (PpIX) and/or GNPs. Ultrasound cavitation activity was determined by recording fluorescence signals from chemical terephthalic acid (TA) dosimeters with or without PpIX and/or GNPs at the frequencies of 0.8 and 2.4 MHz individually and aggregately. To study hydroxyl radicals, experiments were performed with and without hydroxyl radical scavengers mannitol, histidine, and sodium azide. Cavitation activity was amplified by increasing ultrasound intensity and exposure time. The cavitation activity induced by dual ultrasound frequency was remarkably higher than the summation of effects produced by individual frequencies. All three scavengers reduced the fluorescence signal level. The effect of GNPs on intensifying cavitation activity at higher frequency was greater than that of lower frequency. PpIX showed a more effective sonosensitizing property at the lower frequency. Also, estimated synergism at dual frequency irradiation was improved in the presence of GNPs. We found that GNPs increased hydroxyl radical production at 2.4 MHz and that PpIX increased hydroxyl radical production at 0.8 MHz. Dual frequency exposure was more effective than single frequency exposure. PpIX at low frequency and gold nanoparticles at high frequency both enhance sonodynamic treatment efficacy.

2-(Bipiperidin-1-yl)-5-(nitroaryl)-1,3,4-thiadiazoles: Synthesis, evaluation of in vitro leishmanicidal activity, and mechanism of action.

The development of novel leishmanicidal agents that are capable of being replaced by the available therapeutic options has become a priority. In the present study, the synthesis and leishmanicidal activity of a series of 5-(nitroheteroaryl-2-yl)-1,3,4-thiadiazole derivatives are described. All compounds appeared to be potent anti-leishmanial agents against both promastigote and amastigote forms of Leishmania major (L. major). Amongst the synthesized compounds, 2-([1,4'-bipiperidin]-1'-yl)-5-(5-nitrofuran-2-yl)-1,3,4-thiadiazole (IIa) and 1-(5-(1-methyl-5-nitro-1H-imidazole-2-yl)-1,3,4-thiadiazol-2-yl)-4-(piperidine-1-yl) piperidine (IIc) are the most effective. Infection index was statistically declined in the presence of all compounds. The analysis of redox-related factors revealed that exposure of L. major cells to IIa and IIc led to an increase in reactive oxygen species (ROS). Furthermore, two compounds were able to increase ROS and NO levels in infected macrophages in a dose-independent manner. In addition, we showed that these compounds induced cell death in promastigotes. Altogether, our results indicated the anti-leishmanial potential of IIa and IIc is mediated by apoptosis through an imbalance in the redox system resulting in the elevation of ROS. This new class of compound seems to hold great promise for the development of new and useful anti-leishmanial agents.

Truncating Mutations in UBAP1 Cause Hereditary Spastic Paraplegia.

The diagnostic gap for rare neurodegenerative diseases is still considerable, despite continuous advances in gene identification. Many novel Mendelian genes have only been identified in a few families worldwide. Here we report the identification of an autosomal-dominant gene for hereditary spastic paraplegia (HSP) in 10 families that are of diverse geographic origin and whose affected members all carry unique truncating changes in a circumscript region of UBAP1 (ubiquitin-associated protein 1). HSP is a neurodegenerative disease characterized by progressive lower-limb spasticity and weakness, as well as frequent bladder dysfunction. At least 40% of affected persons are currently undiagnosed after exome sequencing. We identified pathological truncating variants in UBAP1 in affected persons from Iran, USA, Germany, Canada, Spain, and Bulgarian Roma. The genetic support ranges from linkage in the largest family (LOD = 8.3) to three confirmed de novo mutations. We show that mRNA in the fibroblasts of affected individuals escapes nonsense-mediated decay and thus leads to the expression of truncated proteins; in addition, concentrations of the full-length protein are reduced in comparison to those in controls. This suggests either a dominant-negative effect or haploinsufficiency. UBAP1 links endosomal trafficking to the ubiquitination machinery pathways that have been previously implicated in HSPs, and UBAP1 provides a bridge toward a more unified pathophysiology.